Intraperitoneal and System Chemotherapy Versus XELOX as First-line Chemotherapy for mCRC

Inclusion Criteria: Patients must have histologically confirmed adenocarcinoma of clorectal with inoperablelocally advanced or metastatic disease, not amenable to curative therapy. Patients must have measurable disease, according to the Response Evaluation Criteria inSolid Tumors (RECIST, v1.1), assessed using imaging techniques (CT or MRI). Women of childbearing potential must be non-pregnant (negative pregnancy test within 72hours prior to chemotherapy, postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential) and nonlactating, and men andwomen must be willing to exercise an effective form of birth control (abstinence/contraception) while on study and for 6 months after therapy completed EasternCooperative Oncology Group (ECOG) Performance status 0, 1 or 2. Absolute neutrophil count (ANC) >=1,500/ul Platelets (PLT) >=75,000/ul Serum bilirubin <= 1.5 × upper limit of normal (ULN) Aspartate transaminase (AST) or alanine aminotransferase (ALT) <= 2.5 × ULN (or <= 5 × ULN in patients with liver metastases) Alkaline phosphatase <= 2.5 × ULN (or <= 5 × ULNin patients with liver metastases, or <= 10 × ULN in patients with bone but no livermetastases) Albumin >= 25 g/L. Creatinine clearance >= 60 mL/min. Life expectancy of atleast 3 months. Signed informed consent.

Exclusion Criteria: Previous chemotherapy for advanced/metastatic disease (prior adjuvant/neoadjuvant therapyis allowed if at least 6 months has elapsed between completion of adjuvant/neoadjuvanttherapy and enrolment into the study). Patients with active (significant or uncontrolled) gastrointestinal bleeding. Residualrelevant toxicity resulting from previous therapy (with the exception of alopecia), e.g.neurological toxicity ≥ grade 2 NCI-CTCAE 4.0. Other malignancy within the last 5 years, except for carcinoma in situ of the cervix, orbasal cell carcinoma. History of documented congestive heart failure; angina pectoris requiringmedication;evidence of transmural myocardial infarction on ECG; poorly controlledhypertension (systolic BP > 180 mmHg or diastolic BP > 100 mmHg); clinically significantvalvular heart disease; or high risk uncontrollable arrhythmias. Baseline left ventricular ejection fraction (LVEF) < 50% (measured by echocardiography orMUGA). Patients with dyspnoea at rest due to complications of advanced malignancy or otherdisease, or who require supportive oxygen therapy. Patients receiving chronic or high dose corticosteroid therapy. (Inhaled steroids and shortcourses of oral steroids for anti-emesis or as an appetite stimulant are allowed). Clinically significant hearing abnormality. Known dihydropyrimidine dehydrogenase (DPD)deficiency. History or clinical evidence of brain metastases. Serious uncontrolled systemicintercurrent illness, e.g. infections or poorly controlled diabetes. Positive serum pregnancy test in women of childbearing potential. Received anyinvestigational drug treatment within 4 weeks of start of study treatment. Radiotherapy within 4 weeks of start of study treatment (2 week interval allowed ifpalliative radiotherapy given to bone metastatic site peripherally and patient recoveredfrom any acute toxicity;prior adjuvant radiotherapy is allowed if complete at least 6months ). Major surgery within 4 weeks of start of study treatment, without complete recovery. Patients with known active infection with HIV, hepatitis B virus (HBV), or hepatitis Cvirus (HCV). Known hypersensitivity to any of the study drugs.